ZT-12-037-01

ZT-12-037-01 is a STK19-targeted inhibitor, has a high-affinity interaction with STK19 protein and inhibits oncogenic NRAS-driven melanocyte malignant transformation. ZT-12-037-01 is an ATP-competitive inhibitor, inhibiting phosphorylation of NRAS (major isoform of Ras family) with an IC50 of 24 nM[1].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Ras

ZT-12-037-01 (3 μM; 14 days) significantly inhibits mutant NRAS-STK19-driven melanocyte colony formation and proliferation[1]. ZT-12-037-01 (0-3 μM) has an inhibitory effects of ZT-12-037-01 on STK19WT and STK19D89N-activated NRAS phosphorylation in HPMs[1]. Cell Proliferation Assay[1] Cell Line: CDK4 (R24C) melanocyte cells; hTERT melanocyte cells; p53DD melanocyte cells Concentration: 3 μM Incubation Time: 14 days Result: Inhibited melanocyte proliferation. Western Blot Analysis[1] Cell Line: STK19WT and STK19D89N Concentration: 0 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Time: Result: Inhibited NRAS phosphorylation.

ZT-12-037-01 (injection subcutaneously; 25-50 mg/kg; once daily; 21 days) inhibits growth of SK-MEL-2 xenograft melanoma and the sections of tumors indicates induction of apoptosis by increasing cleaved caspase-3[1]. Animal Model: SK-MEL-2 xenograft melanoma nude mice with hTERT/p53DD/CDK4(R24C) melanocytes[1] Dosage: 25 mg/kg; 50 mg/kg Administration: Injected subcutaneously; 21 days Result: Inhibited growth of SK-MEL-2 xenograft melanoma.

[1]. Yin C, et al. Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis. Cell. 2019 Feb 21;176(5):1113-1127.e16.